S-adenosyl-L-methionine (hereinafter referred to as SAMe) occurs widely in living organisms. SAMe is a water-soluble physiologically active substance playing a key role as a methyl donor involved in the methylation by a wide range of transmethylase in the synthesis and metabolism of nucleic acid, neurotransmitter, phospholipid, hormone, protein, or the like. SAMe is observed in almost all human cells, serves as a cofactor in various biochemical reactions, and is metabolized through three metabolic pathways: transmethylation, transsulfuration, and transaminopropylation. For example, SAMe is an essential substance for the maintenance of cartilage and the biosynthesis of brain chemicals. A recent function study has reported that SAMe has a therapeutic effect on fatty liver, hyperlipemia, arteriosclerosis, insomnia, alcoholic hepatitis, senile dementia, and the like. As just described, SAMe is an important physiologically active substance and is widely used in Euramerican countries as a therapeutic agent for depression, liver disorder, arthritis, and the like or as a health food.
Therefore, it is strongly desired that SAMe be produced and supplied conveniently and inexpensively. Conventionally, the well-known methods of producing SAMe include a fermentation method of using a culture medium containing L-methionine as a precursor, an enzymatic synthesis method of allowing substrates: adenosine 5′-triphosphate (ATP) and L-methionine to interact with SAMe synthase (methionine adenosyltransferase) isolated and purified from microorganisms and a chemical synthesis method.
In the enzymatic synthesis method, SAMe is enzymatically synthesized by allowing substrates: adenosine 5′-triphosphate (ATP) and L-methionine to interact with SAMe synthase (methionine adenosyltransferase) isolated and purified from microorganisms. This method has an advantage that SAMe is accumulated in large quantities and not required to be extracted from microorganism cells, as compared with the fermentation method. However, this method has various problems including the complex preparation of the enzymes, the low activity of obtained enzymes, the necessity of removing interfering substances, such as ATPase, and the extremely high cost of ATP as a substrate, and therefore cannot necessarily be a practical method.
In addition, the recent progress of genetic engineering has led these enzymes to be prepared more conveniently by using cloned SAMe synthase genes so as to solve the problems involved in the preparation of enzymes. However, high-cost ATP still needs to be used as a substrate, and other practical problems have not been solved.
Furthermore, SAMe is thermolabile and easily degradable even at normal temperature, this presenting a major obstacle to its application to a medicine and a health food. To eliminate this problem, numerous attempts have been made to improve the storage stability. For example, a method is commonly used in which SAMe composition obtained by the above-mentioned production method is purified through chromatography or the like, and then converted into a salt of sulfuric acid, p-toluenesulfonic acid, or butanedisulfonic acid to stabilize SAMe, or in which the purified SAMe is added with an additive to provide a stabilized SAMe composition. These methods require great time and expense and therefore have extremely difficulty in producing and providing important SAMe inexpensively as a therapeutic agent and a health food.
Recently, studies have been made on SAMe-containing microorganisms (for example, see Non-patent Document 1) and SAMe-containing microorganism extracts by using orally available microorganisms having an ability to produce SAMe more conveniently and more inexpensively with fewer steps of purification (for example, see Patent Documents 1-4 and Non-Patent Document 2). At the present time, however, SAMe-containing microorganism extracts involve a problem of lower storage stability than purified SAMe and SAMe compositions.